Protective effects of zinc salts on TPA-induced hepatic and brain lipid peroxidation, glutathione depletion, DNA damage and peritoneal macrophage activation in mice.
1. The comparative protective abilities of zinc L-methionine, zinc DL-methionine, zinc sulfate, zinc gluconate, L-methionine, DL-methionine, and vitamin E succinate (VES) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lipid peroxidation, DNA fragmentation, and glutathione depletion in the hepatic and brain tissues, and production of reactive oxygen species by peritoneal macrophages were assessed. In addition, mice were fed a zinc-deficient diet for 5 weeks, and treated with TPA and/or zinc L-methionine or zinc DL-methionine, and similar studies were conducted. 2. The zinc-deficient diet induced oxidative stress in the hepatic and brain tissues as well as in the peritoneal macrophages as evidenced by significantly enhanced lipid peroxidation. DNA fragmentation, glutathione depletion, and production of reactive oxygen species. 3. Treatment of mice with zinc L-methionine, zinc DL-methionine, and VES decreased TPA-induced reactive oxygen species production as evidenced by significant decreases in chemiluminescence in peritoneal macrophages by approximately 45%, 31%, and 47%, respectively, and cytochrome c reduction by approximately 54%, 35%, and 41%, respectively, as compared with control values. Similar results were observed with liver and brain lipid peroxidation, DNA fragmentation, and glutathione depletion. 4. Zinc salts and antioxidants provided significant protection against TPA-induced oxidative damage. Zinc L-methionine provided the best protection.
Bagchi
D
D
School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178, USA.
Vuchetich
P J
PJ
Bagchi
M
M
Tran
M X
MX
Krohn
R L
RL
Ray
S D
SD
Stohs
S J
SJ
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004249:DNA Damage; D004347:Drug Interactions; D005260:Female; D005942:Gluconates / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008163:Luminescent Measurements; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D008715:Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology; D017967:Zinc Compounds / Q000494:pharmacology*; D019287:Zinc Sulfate / Q000494:pharmacology
D003574:Cytochrome c Group; D005942:Gluconates; D009942:Organometallic Compounds; D017967:Zinc Compounds; D014810:Vitamin E; C074508:zinc methionine; D019287:Zinc Sulfate; D008715:Methionine; D005978:Glutathione; D013755:Tetradecanoylphorbol Acetate; D024505:Tocopherols; C030691:gluconic acid